From induction to movement - a detailed biophysical model for TMS motor activation

• Applicants: Professor Dr. Thomas Knösche; Dr.-Ing. Konstantin Weise
• Subject Area: Biomedical Systems Technology ; Experimental and Theoretical Network Neuroscience
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557520244

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) elicits muscle activity that can be observed by measuring motor evoked potentials (MEP). This procedure is an important tool for studying the central motor pathways. The transformation from TMS induced fields to MEPs recorded from peripheral muscles comprises multiple steps. The time-varying magnetic field induces a dynamic electric field in the neural tissue, impacting motor neurons’ membrane potentials and changing their activity. As a result, action potential volleys are generated and sent down the pyramidal axons to circuits in the spinal cord. There, they are further processed and elicit signals traveling down the peripheral nerves to the muscles. Finally, muscle fiber action potentials are elicited that cause muscle contraction and MEPs measurable on the skin surface. This complex processing chain is only partly understood. Therefore, conclusions from such experiments remain fuzzy and speculative. Here we plan to develop an experimental and modeling framework to study this process in its entirety. Apart from recording hand muscle activity in response to stimulation, we also perform non-invasive observations of descending spike volleys (D- and I-waves) via surface electrodes placed on head, neck, back, and arm. Stimulation and all measurements are linked together by biophysical modeling, taking into account all available knowledge about the anatomy and physiology of the brain and the cortico-spinal-peripheral pathways. This model will comprise the following steps: (1) accurate prediction of the effective electric field, including a novel algorithm correcting for the discrepancy between macroscopic and microscopic fields; (2) localizing the stimulated neurons using a previously developed regression technique; (3) developing a detailed model how electric field changes impact the states of cortical neurons and the dynamics of cortical circuits, thus generating D and I waves; (4) developing a model of signal propagation along central and peripheral fiber pathways accounting for signal dispersion and ephaptic coupling; (5) building a volume conductor model of the neck region in order to link spike volleys in the spinal cord to surface recordings; (6) modeling dynamic processes in the spinal cord circuitry; (7) a numerical model of the hand muscle and the generation of MEPs. As a result, we obtain a modeling framework, which is individually tunable using anatomical data and physiological recordings, and offers a powerful testbed for theories of the motor system in health and disease. For example, projecting alterations of MEP and/or EEG data due to a motor disorder to the parameters of the model would provide insight into the mechanism of the disease and possible treatment options.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Partner Organisation: Czech Science Foundation
• Cooperation Partner: Dr. Vincent Chien